Faculty Bibliography

BACKGROUND:The scarcity of organs available for transplantation has increased attempts to augment transplantation by utilizing obese living kidney donors. The literature has suggested that these donors have increased risks postdonation. Not surprising, the threshold for living kidney donor approval among obese persons is typically higher and the process more costly. Therefore, a screening tool to predict the likelihood of approval among obese living kidney donor candidates was created. METHODS:A single-center retrospective study was performed among obese (body mass index ≥ 30 kg/m2) living kidney donor candidates evaluated in clinic (January 1, 2012, to December 31, 2017). Approved candidates were compared with those not approved using multivariable logistic regression, and a prediction tool was generated. RESULTS:Among 389 obese living kidney donor candidates, there were no significant differences in sex or race and ethnicity by approval status. However, nonapproved candidates had a higher prevalence of metabolic syndrome. In the prediction model, glucose impairment and hypertension were most predictive of nonapproval. CONCLUSION:Among obese living kidney donor candidates, several metabolic syndrome components were associated with decreased odds of approval. This tool may serve as a useful initial screening for obese living kidney donor candidates, permitting more cost-effective evaluation processes. The tool could also be used to promote expeditious interventions in the preclinical setting, including weight management programs, to improve the likelihood of donation and postdonation outcomes.

OBJECTIVE:In this study, we sought to assess likelihood of living donor kidney transplantation (LDKT) within a single-center kidney transplant waitlist, by race and sex, after implementation of an incompatible program. SUMMARY BACKGROUND DATA:Disparities in access to LDKT exist among minority women and may be partially explained by antigen sensitization secondary to prior pregnancies, transplants, or blood transfusions, creating difficulty finding compatible matches. To address these and other obstacles, an incompatible LDKT program, incorporating desensitization and kidney paired donation, was created at our institution. METHODS:A retrospective cohort study was performed among our kidney transplant waitlist candidates (n = 8895). Multivariable Cox regression was utilized, comparing likelihood of LDKT before (era 1: 01/2007-01/2013) and after (era 2: 01/2013-11/2018) implementation of the incompatible program. Candidates were stratified by race [white vs minority (nonwhite)], sex, and breadth of sensitization. RESULTS:Program implementation resulted in the nation's longest single-center kidney chain, and likelihood of LDKT increased by 70% for whites [adjusted hazard ratio (aHR) 1.70; 95% confidence interval (CI), 1.46-1.99] and more than 100% for minorities (aHR 2.05; 95% CI, 1.60-2.62). Improvement in access to LDKT was greatest among sensitized minority women [calculated panel reactive antibody (cPRA) 11%-49%: aHR 4.79; 95% CI, 2.27-10.11; cPRA 50%-100%: aHR 4.09; 95% CI, 1.89-8.82]. CONCLUSIONS:Implementation of an incompatible program, and the resulting nation's longest single-center kidney chain, mitigated disparities in access to LDKT among minorities, specifically sensitized women. Extrapolation of this success on a national level may further serve these vulnerable populations.

OBJECTIVE:To develop and validate an integrative system to predict long term kidney allograft failure. DESIGN:International cohort study. SETTING:Three cohorts including kidney transplant recipients from 10 academic medical centres from Europe and the United States. PARTICIPANTS:Derivation cohort: 4000 consecutive kidney recipients prospectively recruited in four French centres between 2005 and 2014. Validation cohorts: 2129 kidney recipients from three centres in Europe and 1428 from three centres in North America, recruited between 2002 and 2014. Additional validation in three randomised controlled trials (NCT01079143, EudraCT 2007-003213-13, and NCT01873157). MAIN OUTCOME MEASURE:Allograft failure (return to dialysis or pre-emptive retransplantation). 32 candidate prognostic factors for kidney allograft survival were assessed. RESULTS:Among the 7557 kidney transplant recipients included, 1067 (14.1%) allografts failed after a median post-transplant follow-up time of 7.12 (interquartile range 3.51-8.77) years. In the derivation cohort, eight functional, histological, and immunological prognostic factors were independently associated with allograft failure and were then combined into a risk prediction score (iBox). This score showed accurate calibration and discrimination (C index 0.81, 95% confidence interval 0.79 to 0.83). The performance of the iBox was also confirmed in the validation cohorts from Europe (C index 0.81, 0.78 to 0.84) and the US (0.80, 0.76 to 0.84). The iBox system showed accuracy when assessed at different times of evaluation post-transplant, was validated in different clinical scenarios including type of immunosuppressive regimen used and response to rejection therapy, and outperformed previous risk prediction scores as well as a risk score based solely on functional parameters including estimated glomerular filtration rate and proteinuria. Finally, the accuracy of the iBox risk score in predicting long term allograft loss was confirmed in the three randomised controlled trials. CONCLUSION:An integrative, accurate, and readily implementable risk prediction score for kidney allograft failure has been developed, which shows generalisability across centres worldwide and common clinical scenarios. The iBox risk prediction score may help to guide monitoring of patients and further improve the design and development of a valid and early surrogate endpoint for clinical trials. TRIAL REGISTRATION:Clinicaltrials.gov NCT03474003.

Importance:In light of the growing population of older adults in the United States, older donors (aged ≥70 years) represent an expansion of the donor pool; however, their organs are underused. Liver grafts from older donors were historically associated with poor outcomes and higher discard rates, but clinical protocols, organ allocation, and the donor pool have changed in the past 15 years. Objective:To evaluate trends in demographics, discard rates, and outcomes among older liver donors and transplant recipients of livers from older donors in a large national cohort. Design, Setting, and Participants:Prospective cohort study of 4127 liver grafts from older donors and 3350 liver-only recipients of older donor grafts and 78 990 liver grafts from younger donors (aged 18-69 years) and 64 907 liver-only recipients of younger donor grafts between January 1, 2003, and December 31, 2016, in the United States. The Scientific Registry of Transplant Recipients, which includes data on all transplant recipients in the United States that are submitted by members of the Organ Procurement and Transplantation Network, was used. Exposures:Year of liver transplant and age of liver donor. Main Outcomes and Measures:Odds of graft discard and posttransplant outcomes of all-cause graft loss and mortality. Results:In this study, 4127 liver grafts from older donors were recovered for liver transplant across the study period (2003-2016); 747 liver grafts from older donors were discarded, and 3350 liver grafts from older donors were used for liver-only recipients. After adjusting for donor characteristics other than age and accounting for Organ Procurement Organization-level variation, liver grafts from older donors were more likely to be discarded compared with liver grafts from younger donors in 2003-2006 (adjusted odds ratio [aOR], 1.97; 95% CI, 1.68-2.31), 2007-2009 (aOR, 2.55; 95% CI, 2.17-3.01), 2010-2013 (aOR, 2.04; 95% CI, 1.68-2.46), and 2013-2016 (aOR, 2.37; 95% CI, 1.96-2.86) (P < .001 for all). Transplants of liver grafts from older donors represented a progressively lower proportion of all adult liver transplants, from 6.0% (n = 258 recipients) in 2003 to 3.2% (n = 211 recipients) in 2016 (P = .001). However, outcomes in recipients of grafts from older donors improved over time, with 40% lower graft loss risk (adjusted hazard ratio, 0.60; 95% CI, 0.53-0.68; P < .001) and 41% lower mortality risk (adjusted hazard ratio, 0.59; 95% CI, 0.52-0.68; P < .001) in 2010 through 2016 vs 2003 through 2009; these results were beyond the general temporal improvements in graft loss (interaction P = .03) and mortality risk (interaction P = .04) among recipients of liver grafts from younger donors. Conclusions and Relevance:These findings show that from 2003 to 2016, liver graft loss and mortality among recipients of liver grafts from older donors improved; however, liver graft discard from older donors remained increased and the number of transplants performed with liver grafts from older donors decreased. Expansion of the donor pool through broader use of liver grafts from older donors might be reasonable.

Transplant surgery is a predominantly male specialty with high burnout rates. There are currently limited data regarding how programs can attract a diverse applicant pool to the field of transplant surgery. This study evaluated the effect of an Organ Procurement Experience elective on preclinical medical students' perceptions of transplant surgery in a prospective, longitudinal study. Preclinical medical students were anonymously surveyed before and after attending a deceased donor organ procurement. Questions focused on the following themes: Personal Beliefs, Personal/Professional Life, Diversity, and Gender Equality. Responses were rated on a five-point Likert scale. Ninety-nine and 45 students completed pre/post-procurement survey, respectively. Post-procurement responses demonstrated increased education about the field (2.1/5 vs 3.89/5, P < 0.001) and perceptions of the personalities and collegiality between surgeons (3.06/5 vs 3.73/5, P = 0.005). Post-procurement, women were less likely to feel that female transplant surgeons are treated differently (3.98/5 vs. 3.45/5, P < 0.017). Post-procurement, 19% agreed that transplant surgeons have a high quality of life. One percent of respondents felt the current gender distribution in transplant surgery is satisfactory. The Organ Procurement Experience significantly improved preclinical students' perceptions of the field. However, there remains a strong concern about quality of life and gender diversity within the field.

The aim of this study was to determine how the Banff antibody-mediated rejection (ABMR) classification for kidney transplantation is interpreted in practice and affects therapy. The Banff Antibody-Mediated Injury Workgroup electronically surveyed clinicians and pathologists worldwide regarding diagnosis and treatment for 6 case-based scenarios. The participants' (95 clinicians and 72 renal pathologists) assigned diagnoses were compared to the Banff intended diagnoses (reference standard). The assigned diagnoses and reference standard differed by 26.1% (SD 28.1%) for pathologists and 34.5% (SD 23.3%) for clinicians. The greatest discordance between the reference standard and clinicians' diagnosis was when histologic features of ABMR were present but donor-specific antibody was undetected (49.4% [43/87]). For pathologists, the greatest discordance was in the case of acute/active ABMR C4d staining negative in a positive crossmatch transplant recipient (33.8% [23/68]). Treatment approaches were heterogeneous but linked to the assigned diagnosis. When acute/active ABMR was diagnosed by the clinician, treatment was recommended 95.3% (SD 18.4%) of the time vs only 77.7% (SD 39.2%) of the time when chronic active ABMR was diagnosed (P < .0001). In conclusion, the Banff ABMR classification is vulnerable to misinterpretation, which potentially has patient management implications. Continued efforts are needed to improve the understanding and standardized application of ABMR classification in the transplant community.